PDL1 expression in inflammatory breast cancer is frequent and predicts for the pathological response to chemotherapy

François Bertucci, Pascal Finetti, Cécile Colpaert, Emilie Mamessier, Maxime Parizel, Luc Dirix, Patrice Viens, Daniel Birnbaum, Steven van Laere, François Bertucci, Pascal Finetti, Cécile Colpaert, Emilie Mamessier, Maxime Parizel, Luc Dirix, Patrice Viens, Daniel Birnbaum, Steven van Laere

Abstract

We retrospectively analyzed PDL1 mRNA expression in 306 breast cancer samples, including 112 samples of an aggressive form, inflammatory breast cancer (IBC). PDL1 expression was heterogeneous, but was higher in IBC than in non-IBC. Compared to normal breast samples, PDL1 was overexpressed in 38% of IBC. In IBC, PDL1 overexpression was associated with estrogen receptor-negative status, basal and ERBB2-enriched aggressive subtypes, and clinico-biological signs of anti-tumor T-cell cytotoxic response. PDL1 overexpression was associated with better pathological response to chemotherapy, independently of histo-clinical variables and predictive gene expression signatures. No correlation was found with metastasis-free and overall specific survivals. In conclusion, PDL1 overexpression in IBC correlated with better response to chemotherapy. This seemingly counterintuitive correlation between expression of an immunosuppressive molecule and improved therapeutic response may be resolved if PDL1 expression is viewed as a surrogate marker of a strong antitumor immune response among patients treated with immunogenic chemotherapy. In such patients, PDL1 inhibition could protect activated T-cells or reactivate inhibited T-cells and improve the therapeutic response, notably when associated with immunogenic chemotherapy.

Keywords: PDL1; chemotherapy; immune response; inflammatory breast cancer; survival.

Conflict of interest statement

CONFLICTS OF INTEREST

The authors have no conflict of interest to declare.

Figures

Figure 1. PDL1 mRNA expression across clinical…
Figure 1. PDL1 mRNA expression across clinical IBC and non-IBC samples
A. Histogram of distribution of PDL1 expression levels (log2) across the 112 IBC samples (log2 scale) after normalization. The red line represents the density curve of distribution. B.PDL1 expression level (log2) reported as a box plot according to the type of samples: IBC and non-IBC. The black horizontal line represents the expression level in normal breast samples, the red and green lines represent the thresholds for “PDL1-high” and “PDL1-low” groups respectively. The p-value is indicated (Student's t-test) are indicated as follows: *, p < 0.05.
Figure 2. Survival in patients with IBC
Figure 2. Survival in patients with IBC
A. Kaplan-Meier MFS (left) and OSS (right) curves in the 85 patients with IBC. B. Similar to (A), but according to the PDL1 expression status (red curve: “PDL1-high” group versus black curve: “PDL1-low” group).

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